Adenolymphoma ; enzymology ; metabolism ; Humans ; Lymphoma, T-Cell ; enzymology ; metabolism ; Lymphoma, T-Cell, Peripheral ; enzymology ; metabolism ; Male ; Middle Aged ; Nitric Oxide Synthase Type I ; metabolism ; Up-Regulation

To verify the spectrum of CD99-expressing lymphoid malignancy, an immunohistochemical study for CD99 was carried out in 182 cases of non-Hodgkin's lymphoma, including 21 lymphoblastic lymphomas, 11 small lymphocytic lymphomas, 9 mantle cell lymphomas, 12 follicular lymphomas, 37 diffuse large B cell lymphomas, 18 Burkitt's lymphomas, 28 NK/T-cell lymphomas, 8 angioimmunoblastic T-cell lymphomas, 23 peripheral T-cell lymphomas, unspecified, and 15 systemic anaplastic large cell lymphomas. CD99 was positive in all T-lymphoblastic lymphomas and in 60% of B-lymphoblastic lymphomas. Majority of T and NK cell lymphomas were negative for CD99, except anaplastic large cell lymphomas (ALCLs). Eight of 15 cases (54%) of ALCLs reacted with anti CD99 antibody. Seven of 10 (70%) ALK positive ALCLs expressed CD99, whereas only 1 of 5 (20%) ALK negative ALCLs were positive. Of the mature B-cell lymphomas, 5.4% (2/37) of diffuse large B cell lymphomas and 11.1% (2/18) of Burkitt's lymphomas expressed CD99. In conclusion, CD99 is infrequently expressed in mature B and T cell lymphomas, except ALK-positive ALCL. High expression of CD99 in ALK-positive ALCL is unexpected finding and its biologic and clinical significances have yet to be clarified.
Antigens, CD/*metabolism ; Blotting, Western ; Cell Adhesion Molecules/*metabolism ; Humans ; Immunohistochemistry ; Lymphoma, Large-Cell/enzymology/*immunology/pathology ; Lymphoma, Non-Hodgkin/enzymology/*immunology/pathology ; Protein-Tyrosine Kinase/immunology/*metabolism

Granzyme B is one of the serine proteases expressed in natural killer (NK) cells and activated cytotoxic T-lymphocytes. To evaluate the usefulness of granzyme B immunoreactivity in the diagnosis of T/NK-cell lymphoma, we studied 69 cases of lymphomas occurring in the upper aerodigestive tract by paraffin-section immunohistochemistry using a commercially available monoclonal antibody to granzyme B (GrB-7). All 19 cases of T/NK-cell lymphomas defined by the expression of CD56 (NHK-1) and one or both T-cell markers (polyclonal CD3 and CD45RO) expressed granular cytoplasmic granzyme B immunoreactivity. Two out of 9 cases of T-cell lymphomas showing no CD56 expression demonstrated strong granzyme B immunoreactivity. No tumor cells among 39 cases of B-cell diffuse large cell lymphomas and 2 cases of null cell diffuse large cell lymphomas were immunoreactive for granzyme B, however a few scattered granzyme B-positive reactive small lymphoid cells were consistently observed. Based on its sensitivity in this study as well as its reactivity in routinely processed tissue sections, even without heat-induced epitope retrieval technique, monoclonal antibody to granzyme B (GrB-7) can be applied as a useful marker in the diagnosis of T/NK-cell lymphomas in conjunction with CD56.
Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Human ; Immunohistochemistry ; Killer Cells/pathology* ; Lymphoma/pathology* ; Lymphoma/enzymology* ; Lymphoma, T-Cell/pathology ; Lymphoma, T-Cell/enzymology* ; Male ; Middle Age ; Serine Endopeptidases/metabolism*

OBJECTIVETo study the difference in expression of TOPK/PBK in lymph nodes between children with malignant lymphoma and those with reactive lymphoid hyperplasia.

METHODSEighty children with malignant lymphoma and twenty children with reactive lymphoid hyperplasia were enrolled as subjects. Immunohistochemistry was used to determine the expression of TOPK/PBK in all the subjects. The expression of TOPK/PBK was compared between the two groups.

RESULTSThe TOPK/PBK-positivity rate was significantly higher in children with malignant lymphoma than in those with reactive lymphoid hyperplasia (P<0.05). There was no significant difference in the TOPK/PBK-positivity rate between the children with Hodgkin's lymphoma and non-Hodgkin's lymphoma (NHL). There were significant differences in the TOPK/PBK-positivity rate among children with different pathological types of NHL (P<0.05): the children with lymphoblastic lymphoma showed the highest TOPK/PBK-positivity rate and those with mature B-cell lymphoma and mature T/NK-cell lymphoma had a similar TOPK/PBK-positivity rate.

CONCLUSIONSThe expression of TOPK/PBK is up-regulated in the lymph nodes of children with malignant lymphoma. The expression level of TOPK/PBK may be related to the pathological type of NHL.

Adolescent ; Child ; Child, Preschool ; Humans ; Infant ; Infant, Newborn ; Lymph Nodes ; enzymology ; Lymphoma ; enzymology ; Mitogen-Activated Protein Kinase Kinases ; analysis ; Pseudolymphoma ; enzymology

Humans ; Lymphoma, Large-Cell, Anaplastic ; diagnosis ; enzymology ; therapy ; Receptor Protein-Tyrosine Kinases

OBJECTIVETo detect the expression level of asparagine synthetase (ASNS) in patients with relapsed or refractory extranodal NK/T cell lymphoma and explore its clinical significance.

METHODSTen patients with relapsed or refractory extranodal NK/T cell lymphoma admitted in our department from January, 2013 to January, 2016 were analyzed. The diagnoses were confirmed by pathological and immunohistochemical examination following failed chemotherapies in all cases. Branched DNA-liquidchip technique (bDNA-LCT) was used for detecting ASNS mRNA expression in paraffin-embedded tissue sections in the 10 cases of relapsed or refractory extranodal NK/T cell lymphoma and in 5 cases of chronic rhinitis. The correlations were analyzed between ASNS expression and the clinicopathological features and outcomes of the patients with failed chemotherapy regimens containing asparaginasum.

RESULTSSix out of the 10 patients with relapsed or refractory extranodal NK/T cell lymphoma died due to diseaseprogression. The expression level of ASNS was significantly higher in the lymphoma tissues than in tissue specimens of chronic rhinitis (P<0.05). The expression level of ASNS was associated with the International Prognostic Index (P=0.023) in patients with relapsed or refractory extranodal NK/T cell lymphoma, and Kaplan-Meier curve showed that a high ASNS expression was correlated with a reduced overall survival and progression-free survival of the patients.

CONCLUSIONAsparaginasum-based chemotherapy regimens are recommended for treatment of relapsed or refractory extranodal NK/T cell lymphoma with low ASNS expressions.

Aspartate-Ammonia Ligase ; metabolism ; Disease-Free Survival ; Humans ; Lymphoma, Extranodal NK-T-Cell ; enzymology ; Recurrence

Gastric CD30-positive anaplastic large-cell lymphoma is a very rare disease. It is sometimes difficult to distinguish it from undifferentiated carcinoma, sarcoma and so on. We report here on a case of primary gastric anaplastic large-cell lymphoma. A 50-yr-old woman complained of epigastric pain and severe chest pain for 1 week. The gastroendoscopic examination revealed geographic mucosal irregularities with shallow ulceration at the antrum. She underwent a total gastrectomy. The gross finding of the resected stomach was an 8 x 4.5 cm sized ulceroinfiltrative lesion at the pyloric antrum along the lesser curvature. The microscopic examination revealed diffuse and solid proliferations of large atypical cells with pleomorphic nuclei. Immunohistochemically, the tumor cells were positive for CD30, vimentin and CD3, and this was a finding compatible with anaplastic large-cell lymphoma. To the best of our knowledge, this is the first such reported case in Korea.
Antigens, CD30/*metabolism ; Female ; Humans ; Immunohistochemistry ; Korea ; Lymphoma, Large-Cell/enzymology/*immunology/*pathology ; Middle Aged ; Protein-Tyrosine Kinase/metabolism ; Stomach Neoplasms/enzymology/*immunology/*pathology

High expression of cellular asparagine synthetase (AS) is a causative factor for the resistance of leukemic cell to L-asparaginase therapy. This study was aimed to find single nucleotide polymorphism (SNPs) in the promotor region of asparagine synthetase (AS) gene and to determine if these SNPs have influence on the transcriptional activity of AS promotor. The DNA sequences of AS promoter (pAS) from 82 leukemic children and 45 controls were determined to screen for SNPs in this region and the AS mRNA level in these samples was quantified using real-time PCR assay. The results indicated that three SNPs were found in the sequenced pAS fragment. They were -239C/T, -92G/A and -62A/T respectively. The frequency of -92A allele was higher in leukemic samples than that in nonleukemic control (P<0.05). The gene expression level differed among the individuals with genotype of the -92G/A SNP, and the descending order was as follows: GA heterozygote > AA homozygote > GG homozygote. It is concluded that some features in leukemia might associate with SNP on -92A locus, and this SNP in pAS can be one of the factors influencing transcriptional activity of AS gene. The existence of the -92A allele variant contributes to a high expression of AS gene.
Aspartate-Ammonia Ligase ; genetics ; Child ; Female ; Humans ; Leukemia, Myeloid, Acute ; enzymology ; genetics ; Male ; Polymorphism, Single Nucleotide ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; enzymology ; genetics ; Promoter Regions, Genetic ; genetics

Molecular target therapy is one of the most popular field of non-small cell lung cancer (NSCLC) treatmnet. Epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearragement are the most important two oncogenic drivers in NSCLC, early studies suggested that EGFR mutations and ALK rearrangements are mutually exclusive, but isolated cases or small sample research with concomitant EGFR and ALK alterations have been constantly reported. The co-occurrence of EGFR mutations and anaplastic lymphoma kinase (ALK) rearrangements constitutes a rare molecular, the frequency of EGFR/ALK co-alterations was about 1%, however, little has been known about clinicopathologic feature and treatment. This review summarized published case report, EGFR and ALK alterations are common in female, Asian origin, never smoker, IV stage, and denocarcinomas. First-line treatment can choose EGFR or ALK tyrosine kinase inhibitors (TKIs). However, studies about the origin and resistance mechanism in EGFR/ALK co-alterations are little, require more experimental and clinical research.
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Anaplastic Lymphoma Kinase ; Carcinoma, Non-Small-Cell Lung ; diagnosis ; enzymology ; genetics ; ErbB Receptors ; genetics ; Humans ; Lung Neoplasms ; diagnosis ; enzymology ; genetics ; Mutation ; Prognosis ; Receptor Protein-Tyrosine Kinases ; genetics

OBJECTIVETo determine whether the high level of asparagine synthetase (AS) expression in childhood acute lymphocytic leukemia (ALL) is associated with an inferior prognosis.

METHODSAS mRNA level in leukemic cells from 53 newly diagnosed ALL children was measured by real time fluorescent quantitative PCR method. Patients were divided into groups according to their relapse risk and outcome, and the AS expression levels in each group were compared. The survival rates in different AS expressing level groups were estimated and compared.

RESULTSThe highest level of AS [median 17.25 (2.48-46. 82)] was observed in children failed remission, intermediate level [14.28 (3.20-54.47)] in relapsed children and the lowest level [5.08 (0.84-54.92)] in children with continuous complete remission (CCR) (P<0.05). The AS mRNA level [14.93 (2.48-54.47)] in children with poor outcome (un-remission and relapsed) was significantly higher than that in children in CCR (P<0.01). The two-year estimated disease free survival was much lower in children with high AS expression (53.8%) than in those with low AS expression (84.6%) (P<0.05).

CONCLUSIONHigh expression of AS is associated with a poor outcome in ALL children.

Adolescent ; Aspartate-Ammonia Ligase ; metabolism ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; enzymology ; Prognosis